Excessive daytime sleepiness (EDS) is a common clinical complaint in the elderly. However, the cause of this problem is largely unknown. Given the high prevalence of EDS, there was much excitement when it was recognized that sleep-disordered breathing (sleep apnea) was also common in elderly subjects (the major clinical consequence of sleep apnea is EDS). Disappointingly, however, subsequent studies in randomly selected elderly have shown only low level, or no, association between the presence of sleep apnea and EDS assessed either subjectively or objectively. This raises the question why the complaint should be so common, but it seems not to be explained by the most likely underlying disease. In this proposal, we argue that we need to develop a different approach for the problem in the elderly. Excessive daytime sleepiness in the elderly is likely to be multifactorial. The most likely pathophysiological mechanism is sleep fragmentation that can result from a number of different causes. These concepts lead us to propose a case- control study, in which we specifically identify as cases elderly subjects who complain of sleepiness. Cases will be identified, using a screening questionnaire, and we will define a case as an individual who indicates a problem with sleepiness on several days per week. In contrast, a control will have no such problem and will report not falling asleep in various active situations. Both cases and controls will have nocturnal sleep studies, tests of daytime function and will complete a full questionnaire to identify the presence, or absence, of various risk factors. Sleep studies will be performed in the subject's apartment. These data will be used to identify the role of different potential risk factors in causing sleepiness in the elderly. Since sleepiness will also be objectively measured, we will, as a secondary analysis, identify subsets of cases and controls with both subjective and objective evidence of sleepiness. This step will be facilitated by us developing appropriate criteria for objective assessment of sleepiness in the elderly. As part of these analyses we plan to develop new metrics of nocturnal sleep disturbance. Traditional measures to describe and quantify sleep-disordered breathing, such as the respiratory disturbance index, may not be optimal for clinical purposes in the elderly. Rather, we need to develop measures related to sleep fragmentation and continuity that incorporate the effect of all pathophysiological processes disturbing sleep. This will allow us to quantify the role of any one specific process, such as sleep apnea. Moreover, by developing multi- variable models we will be able to simulate the effect of treating specific sleep disorders, such as sleep apnea. Thus, this proposal is directed at what we believe is the key clinical question in this field at this time, i.e., are there many, or few, elderly subjects that are likely to benefit from treatment for sleep apnea and how can such subjects be identified? Criteria developed from this study could be the basis for a future intervention trial.